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2016 ; 7
(ä): 473
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Complementary Roles of the Classical and Lectin Complement Pathways in the
Defense against Aspergillus fumigatus
#MMPMID27857715
Rosbjerg A
; Genster N
; Pilely K
; Skjoedt MO
; Stahl GL
; Garred P
Front Immunol
2016[]; 7
(ä): 473
PMID27857715
show ga
Aspergillus fumigatus infections are associated with a high mortality rate for
immunocompromised patients. The complement system is considered to be important
in protection against this fungus, yet the course of activation is unclear. The
aim of this study was to unravel the role of the classical, lectin, and
alternative pathways under both immunocompetent and immunocompromised conditions
to provide a relevant dual-perspective on the response against A. fumigatus.
Conidia (spores) from a clinical isolate of A. fumigatus were combined with
various human serum types (including serum deficient of various complement
components and serum from umbilical cord blood). We also combined this with
inhibitors against C1q, mannose-binding lectin (MBL), and ficolin-2 before
complement activation products and phagocytosis were detected by flow cytometry.
Our results showed that alternative pathway amplified complement on A. fumigatus,
but required classical and/or lectin pathway for initiation. In normal human
serum, this initiation came primarily from the classical pathway. However, with a
dysfunctional classical pathway (C1q-deficient serum), lectin pathway activated
complement and mediated opsonophagocytosis through MBL. To model the
antibody-decline in a compromised immune system, we used serum from normal
umbilical cords and found MBL to be the key complement initiator. In another set
of experiments, serum from patients with different kinds of immunoglobulin
insufficiencies showed that the MBL lectin pathway contribution was highest in
the samples with the lowest IgG/IgM binding. In conclusion, lectin pathway
appears to be the primary route of complement activation in the absence of
anti-A. fumigatus antibodies, whereas in a balanced immune state classical
pathway is the main activator. This suggests a crucial role for the lectin
pathway in innate immune protection against A. fumigatus in immunocompromised
patients.